1-65565601-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_002303.6(LEPR):āc.36T>Cā(p.His12His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000498 in 1,613,942 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002303.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00262 AC: 399AN: 152176Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000716 AC: 180AN: 251272Hom.: 0 AF XY: 0.000530 AC XY: 72AN XY: 135822
GnomAD4 exome AF: 0.000276 AC: 404AN: 1461648Hom.: 0 Cov.: 31 AF XY: 0.000231 AC XY: 168AN XY: 727114
GnomAD4 genome AF: 0.00263 AC: 400AN: 152294Hom.: 2 Cov.: 32 AF XY: 0.00266 AC XY: 198AN XY: 74468
ClinVar
Submissions by phenotype
not specified Benign:2
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Obesity due to leptin receptor gene deficiency Uncertain:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
LEPR-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at